Given the poor prognosis of idiopathic pulmonary fibrosis (IPF) and its acute exacerbation (AE-IPF), the exploration of their prognostic biomarkers is important. Extracellular mitochondrial DNA (mtDNA) acts as a danger-associated molecular pattern which induces inflammatory response. In the field of IPF, mtDNA elevats in plasma and bronchoalveolar lavage fluid (BALF), and plasma mtDNA is related with disease progression or occurrence of AE, while the clinical importance of BALF-mtDNA still remains unclear. In this study, we have evaluated the clinical impact of BALF-mtDNA in IPF patients.

Between 2009 to 2017, BALF samples were collected from IPF patients. Some patients underwent BAL both at baseline and the time of AE. BALF-mtDNA was measured by droplet digital polymerase chain reaction (ddPCR), a novel refined PCR method which can detect small number of targets with higher precision. Other clinical parameters were collected retrospectively.

In 27 patients who underwent BAL both at baseline and the time of AE, BALF-mtDNA was significantly increased at the time of AE. In 91 patients with BAL at baseline, elevated BALF-mtDNA was correlated with smoking status and lower DLCO, while in 38 patients with BAL at the time of AE, it was positively correlated with BALF neutrophils. After adjustment by age, sex, FVC and DLCO (obtained within 6 months before the BAL), BALF-mtDNA ?4234.3 copies/µL at baseline (MST: 42.4 vs. 79.6 months, p<0.001) and ?11194.3 copies/µL at time of AE (MST: 2.6 vs. 20.0 months, p=0.03) were predictive for mortality after the BAL.

In conclusion, BALF-mtDNA was a novel prognostic factor of both IPF and AE-IPF. Especially, it was useful to distinguish survivors and non-survivors of AE-IPF.